Romosozumab Enhances Vertebral Bone Structure in Women With Low Bone Density.

Romosozumab monoclonal antibody treatment works by binding sclerostin and causing rapid stimulation of bone formation while decreasing bone resorption. The location and local magnitude of vertebral bone accrual by romosozumab and how it compares to teriparatide remains to be investigated. Here we analyzed the data from a study collecting lumbar computed tomography (CT) spine scans at enrollment and 12 months post-treatment with romosozumab (210 mg sc monthly, n = 17), open-label daily teriparatide (20 µg sc, n = 19), or placebo (sc monthly, n = 20). For each of the 56 women, cortical thickness (Ct.Th), endocortical thickness (Ec.Th), cortical bone mineral density (Ct.bone mineral density (BMD)), cancellous BMD (Cn.BMD), and cortical mass surface density (CMSD) were measured across the first lumbar vertebral surface. In addition, color maps of the changes in the lumbar vertebrae structure were statistically analyzed and then visualized on the bone surface. At 12 months, romosozumab improved all parameters significantly over placebo and resulted in a mean vertebral Ct.Th increase of 10.3% versus 4.3% for teriparatide, an Ec.Th increase of 137.6% versus 47.5% for teriparatide, a Ct.BMD increase of 2.1% versus a -0.1% decrease for teriparatide, and a CMSD increase of 12.4% versus 3.8% for teriparatide. For all these measurements, the differences between romosozumab and teriparatide were statistically significant (p < 0.05). There was no significant difference between the romosozumab-associated Cn.BMD gains of 22.2% versus 18.1% for teriparatide, but both were significantly greater compared with the change in the placebo group (-4.6%, p < 0.05). Cortical maps showed the topographical locations of the increase in bone in fracture-prone areas of the vertebral shell, walls, and endplates. This study confirms widespread vertebral bone accrual with romosozumab or teriparatide treatment and provides new insights into how the rapid prevention of vertebral fractures is achieved in women with osteoporosis using these anabolic agents. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Effects of Romosozumab Compared With Teriparatide on Bone Density and Mass at the Spine and Hip in Postmenopausal Women With Low Bone Mass.

Romosozumab, a monoclonal antibody that binds sclerostin, has a dual effect on bone by increasing bone formation and reducing bone resorption, and thus has favorable effects in both aspects of bone volume regulation. In a phase 2 study, romosozumab increased areal BMD at the lumbar spine and total hip as measured by DXA compared with placebo, alendronate, and teriparatide in postmenopausal women with low bone mass. In additional analyses from this international, randomized study, we now describe the effect of romosozumab on lumbar spine and hip volumetric BMD (vBMD) and BMC at month 12 as assessed by QCT in the subset of participants receiving placebo, s.c. teriparatide (20 µg once daily), and s.c. romosozumab (210 mg once monthly). QCT measurements were performed at the lumbar spine (mean of L1 and L2 entire vertebral bodies, excluding posterior processes) and hip. One year of treatment with romosozumab significantly increased integral vBMD and BMC at the lumbar spine and total hip from baseline, and compared with placebo and teriparatide (all p < 0.05). Trabecular vertebral vBMD improved significantly and similarly from baseline (p < 0.05) with both romosozumab (18.3%) and teriparatide (20.1%), whereas cortical vertebral vBMD gains were larger with romosozumab compared with teriparatide (13.7% versus 5.7%, p < 0.0001). Trabecular hip vBMD gains were significantly larger with romosozumab than with teriparatide (10.8% versus 4.2%, p = 0.01), but were similar for cortical vBMD (1.1% versus -0.9%, p = 0.12). Cortical BMC gains were larger with romosozumab compared with teriparatide at both the spine (23.3% versus 10.9%, p < 0.0001) and hip (3.4% versus 0.0%, p = 0.03). These improvements are expected to result in strength gains and support the continued clinical investigation of romosozumab as a potential therapy to rapidly reduce fracture risk in ongoing phase 3 studies. © 2016 American Society for Bone and Mineral Research.

Prevalence of Osteoporosis in Women in Buenos Aires Based on Bone Mineral Density at the Lumbar Spine and Femur.

The aim of the study was to report values for osteoporosis (OP) prevalence in Buenos Aires. Bone mineral density (BMD) at different skeletal sites was measured from November 2012 to July 2014. Participants were recruited through a newspaper advertisement inviting women at least 50 yr of age to receive free BMD measurement. After signing an informed consent form, 5448 women living in Buenos Aires and surrounding districts were studied. Lumbar spine (L1-L4), femur neck, and total hip BMDs were measured (Lunar Prodigy, software version 12.3 GE, Madison, WI, USA). OP was defined as a T-score ≤-2.5 at the lumbar spine or the femoral neck. Results showed that 1021 out of 5448 studied subjects (18.7%) had OP at the lumbar spine or the femoral neck. Comparison of age of the population sample with reference data for the general population showed a moderate (+0.6%) increase in prevalence. Prevalence of OP was low, up to the age of 70 yr when based on femoral neck BMD only. Conversely, the prevalence of OP at the lumbar spine, which was reportedly high in women up to the age of 70 yr, tended to level off over that age. The results of the total femur only added a slight (+0.7%) nonsignificant increase to the OP prevalence. A total 346,500 out of 1,853,000 women aged 50+ yr in Buenos Aires had OP at the lumbar spine or femoral neck, whereas only 163,500 had OP at the upper femur, reducing the number by 53%. The present study assessed OP prevalence in the most densely populated urban area in Argentina. The results are similar to those reported for Caucasian populations in the United States and Canada. As measurement of only the BMD of femoral neck overlooks the diagnosis in half of the women, future studies should include measurement of the lumbar spine in combination with the femoral neck for a more accurate estimation of OP prevalence.

Prevalencia de osteoporosis: discrepancia de acuerdo a las áreas esqueléticas de medición / Prevalence of osteoporosis: discrepancy according to the skeletal areas of evaluation

Existe discrepancia en la elección de las áreas esqueléticas a evaluar para determinar la prevalencia de osteoporosis (OP). La International Society for Clinical Densitometry sugiere evaluar la columna lumbar (CL) y el fémur proximal (FT), mientras que la International Osteoporosis Foundation (IOF) sugiere medir solo el cuello femoral (CF). La estimación de la prevalencia de OP evaluada solo por CF en mujeres mayores de 50 años de Buenos Aires mostró un sub-diagnóstico del 53%. Objetivo: analizar la discrepancia en la prevalencia de OP, según el área esquelética evaluada por DXA, en los estudios internacionales disponibles. Materiales y Métodos: Se incluyeron los trabajos publicados en la literatura internacional, en idioma inglés que contenían: 1. Medición simultánea de CL y CF. 2. Análisis por décadas a partir de los 50 años y hasta por lo menos la década 70-79. 3. Diagnóstico densitométrico de osteoporosis con el criterio de la OMS: T-score ≤-2.5. Resultados: fueron incluidos doce estudios. La evaluación de estos estudios arrojó un sub-diagnóstico global del 52 % si la prevalencia de OP fuera estimada solo por la densidad mineral ósea (DMO) de CF. Cuando analizamos por décadas la sub-estimación fue del 75% en la 6a década, 58% en la 7a década y del 22% en 8a década, mostrando claramente que el subdiagnóstico disminuye a medida que aumenta la edad y desaparece después de los 80 años. Conclusión: Estos resultados señalan que la prevalencia de OP debe ser determinada a través de la evaluación de la DMO de ambas áreas esqueléticas: CL y CF. (AU)

There is discrepancy in the election of skeletal areas to be measured to determine the prevalence of osteoporosis.The International Society for Clinical Densitometry suggests evaluating the lumbar spine and proximal femur, while the International Osteoporosis Foundation (IOF) suggests measuring only the femoral neck.The estimate of the prevalence of osteoporosis (OP) evaluated only for femoral neck (FN) in women over 50 years of Buenos Aires showed underdiagnosis of 53%. Objective: To analyze the discrepancy on the prevalence of OP, according to the skeletal area evaluated by DXA, in international studies. Material and Methods: We included the works published in the international English literature that contained: 1- Simultaneous measurement of lumbar spine (LS) and femoral neck (FN). 2- Analysis for decades from 50 years and up to at least the decade 70-79. 3- Densitometric diagnosis of osteoporosis according to WHO: T-score ≤-2.5. Results: Twelve studies were included. The evaluation of these studies showed an overall underdiagnosis of 52% if the prevalence of OP was estimated only for bone mineral density of the femoral neck.When we analyzed for decades the underestimation was 75% in the sixth decade, 58% in the seventh and 22% in the eighth decade, clearly showing that the underdiagnosis decreases as age increases and disappears after 80 years. Conclusion: This over-all review of 12 studies indicates that lumbar spine as well as femoral neck should be assessed by DXA to determine the prevalence of osteoporosis. (AU)

Regression of an ossifying fibroma of the tibia after a fracture involving the lesion. Possible role of the periostina.

Ossifying fibroma (OF) of the long bones is a benign fibro-osseous lesion typically seen in the first decade of life. OF usually progresses until the age of 10 years, but is occasionally found to regress spontaneously after puberty. The pathogenesis of OF is unknown; however, it has been suggested that the basic defect is in the periosteum. We present the radiological course of an OF of the tibia in a young patient, showing a rapid almost complete regression of the lesion after a tibial fracture at the lesion site. We postulate that the fracture-induced activation of the periosteum in a growing skeleton was fundamental to the regression of the lesion.

Impact of denosumab on the peripheral skeleton of postmenopausal women with osteoporosis: bone density, mass, and strength of the radius, and wrist fracture.

OBJECTIVE: The aim of this study was to report the effects of denosumab on radius cortical and trabecular bone density, mass, and strength, and wrist fracture incidence in the FREEDOM (Fracture REduction Evaluation of Denosumab in Osteoporosis every 6 Months) study. METHODS: In the FREEDOM study, postmenopausal women with osteoporosis (N = 7,808) received placebo or 60 mg of denosumab every 6 months for 36 months. Radius bone mineral density (BMD), bone mineral content, and strength (polar moment of inertia) were evaluated in two prespecified substudies using dual-energy x-ray absorptiometry (placebo, n = 209; denosumab, n = 232) or quantitative CT (placebo, n = 48; denosumab, n = 62). Prespecified analysis assessed wrist fracture incidence in all FREEDOM participants (placebo, N = 3,906; denosumab, N = 3,902), and post hoc subgroup analyses evaluated those with higher fracture risk (baseline femoral neck T-score ≤-2.5; placebo, N = 1,406; denosumab, N = 1,384). RESULTS: Denosumab significantly increased areal BMD (assessed by dual-energy x-ray absorptiometry) and volumetric BMD, bone mineral content, and polar moment of inertia (assessed by quantitative CT), compared with placebo, in radius cortical and trabecular bone at all time points evaluated (all P < 0.05). Wrist fracture incidence was 2.9% for placebo and 2.5% for denosumab (relative risk reduction, 16%; P = 0.21) on month 36. Participants with a femoral neck T-score of -2.5 or lower were at increased risk for wrist fracture, and denosumab significantly reduced wrist fracture incidence compared with placebo (placebo, 4.0%; denosumab, 2.4%; relative risk reduction, 40%; absolute risk reduction, 1.6%; P = 0.03). CONCLUSIONS: Denosumab significantly improves radius bone density, mass, and strength compared with placebo. In higher-risk women, denosumab significantly reduces wrist fracture risk.

Increase in android fat mass with age in healthy women with normal body mass index.

Body fat distribution is gender specific: men tend to accumulate adipose tissue in the android region, whereas women tend to do so in the gynoid region. The aim of the study was to assess total fat mass (TFM), android fat (AF), and gynoid fat (GF) mass in a selected group of healthy adult women with normal body mass index (BMI) to evaluate variations in fat distribution. Seventy-seven women (20--69yr of age) with BMI values between ≥18.5 and ≤24.9kg/m(2) were included. TMF, AF, GF, and the AF to GF ratio (A:G) were assessed using dual-energy X-ray absorptiometry. Results showed an increase in AF after the fifth decade of life (D), which reached statistical significance in the sixth and seventh decades (p<0.05--0.008), a 33% increase in kg of AF between the fourth and seventh and a 20% increase in A:G between the third and the seventh, with no significant changes in TFM and GF. In normal BMI women, age appears to be associated with changes in fat mass distribution with an increase in AF, which might have potential deleterious health consequences, after the fifth D.

Effects of intravenous ibandronate injection on renal function in women with postmenopausal osteoporosis at high risk for renal disease--the DIVINE study.

The Designed for intravenous (IV) Ibandronate reNal safety Evaluation (DIVINE) study was a 1-year prospective, randomized, open label, multi-center study that evaluated the renal safety of quarterly (every 3 months) ibandronate IV injection given over 15-30s compared with infusion given over 15 min, and weekly oral alendronate, in women with postmenopausal osteoporosis (PMO) at increased risk for renal disease. Both injection and infusion of IV ibandronate showed comparable safety to alendronate, with only small changes in serum creatinine (sCr) for each treatment group, and AEs were generally comparable between groups. All three treatments had similar effects on renal function, measured by change in baseline of the glomerular filtration rate; the ibandronate IV injection group was noninferior to the ibandronate IV infusion and weekly oral alendronate groups at 9 months, with similar results at 1 year. The results of this study demonstrate the profile of IV ibandronate, which allows it to be dosed as an IV injection in the primary care setting without the need for an infusion, even in patients with pre-existing hypertension or diabetes mellitus.

Zoledronic acid and clinical fractures and mortality after hip fracture.

BACKGROUND: Mortality is increased after a hip fracture, and strategies that improve outcomes are needed. METHODS: In this randomized, double-blind, placebo-controlled trial, 1065 patients were assigned to receive yearly intravenous zoledronic acid (at a dose of 5 mg), and 1062 patients were assigned to receive placebo. The infusions were first administered within 90 days after surgical repair of a hip fracture. All patients (mean age, 74.5 years) received supplemental vitamin D and calcium. The median follow-up was 1.9 years. The primary end point was a new clinical fracture. RESULTS: The rates of any new clinical fracture were 8.6% in the zoledronic acid group and 13.9% in the placebo group, a 35% risk reduction with zoledronic acid (P=0.001); the respective rates of a new clinical vertebral fracture were 1.7% and 3.8% (P=0.02), and the respective rates of new nonvertebral fractures were 7.6% and 10.7% (P=0.03). In the safety analysis, 101 of 1054 patients in the zoledronic acid group (9.6%) and 141 of 1057 patients in the placebo group (13.3%) died, a reduction of 28% in deaths from any cause in the zoledronic acid group (P=0.01). The most frequent adverse events in patients receiving zoledronic acid were pyrexia, myalgia, and bone and musculoskeletal pain. No cases of osteonecrosis of the jaw were reported, and no adverse effects on the healing of fractures were noted. The rates of renal and cardiovascular adverse events, including atrial fibrillation and stroke, were similar in the two groups. CONCLUSIONS: An annual infusion of zoledronic acid within 90 days after repair of a low-trauma hip fracture was associated with a reduction in the rate of new clinical fractures and with improved survival. (ClinicalTrials.gov number, NCT00046254 [ClinicalTrials.gov].).

Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis.

BACKGROUND: A single infusion of intravenous zoledronic acid decreases bone turnover and improves bone density at 12 months in postmenopausal women with osteoporosis. We assessed the effects of annual infusions of zoledronic acid on fracture risk during a 3-year period. METHODS: In this double-blind, placebo-controlled trial, 3889 patients (mean age, 73 years) were randomly assigned to receive a single 15-minute infusion of zoledronic acid (5 mg) and 3876 were assigned to receive placebo at baseline, at 12 months, and at 24 months; the patients were followed until 36 months. Primary end points were new vertebral fracture (in patients not taking concomitant osteoporosis medications) and hip fracture (in all patients). Secondary end points included bone mineral density, bone turnover markers, and safety outcomes. RESULTS: Treatment with zoledronic acid reduced the risk of morphometric vertebral fracture by 70% during a 3-year period, as compared with placebo (3.3% in the zoledronic-acid group vs. 10.9% in the placebo group; relative risk, 0.30; 95% confidence interval [CI], 0.24 to 0.38) and reduced the risk of hip fracture by 41% (1.4% in the zoledronic-acid group vs. 2.5% in the placebo group; hazard ratio, 0.59; 95% CI, 0.42 to 0.83). Nonvertebral fractures, clinical fractures, and clinical vertebral fractures were reduced by 25%, 33%, and 77%, respectively (P<0.001 for all comparisons). Zoledronic acid was also associated with a significant improvement in bone mineral density and bone metabolism markers. Adverse events, including change in renal function, were similar in the two study groups. However, serious atrial fibrillation occurred more frequently in the zoledronic acid group (in 50 vs. 20 patients, P<0.001). CONCLUSIONS: A once-yearly infusion of zoledronic acid during a 3-year period significantly reduced the risk of vertebral, hip, and other fractures. (ClinicalTrials.gov number, NCT00049829.)

Sustained vertebral fracture risk reduction after withdrawal of teriparatide in postmenopausal women with osteoporosis.

BACKGROUND: Teriparatide (recombinant human parathyroid hormone [1-34]) reduces fracture risk in postmenopausal women with osteoporosis. We assessed the safety and incidence of new vertebral fractures after withdrawal of teriparatide. METHODS: This study is a follow-up to the Fracture Prevention Trial (FPT), a randomized, placebo-controlled study of postmenopausal women with osteoporosis treated with teriparatide (20 or 40 microg) once daily for a mean of 18 months. More than 90% of the women remaining at the end of the FPT continued into the follow-up study (n = 1262). Patients and investigators were unblinded to original treatment group assignment. Women were treated according to standard clinical practice, including elective use of osteoporosis drugs. New vertebral fractures were determined by semiquantitative scoring of lateral thoracic lumbar spine radiographs 18 months after the end of the FPT. RESULTS: During the follow-up study, the reduction in fracture risk associated with previous treatment with teriparatide, 20 and 40 microg, was 41% (P = .004) and 45% (P = .001), respectively, vs placebo. The absolute reduction from the FPT baseline to the 18-month follow-up visit was 13% for both doses. Osteoporosis drugs were used by 47% of women during follow-up, with greater use in the former placebo group (P = .04); nevertheless, persistent fracture protection of previous teriparatide therapy was evident. Post hoc analysis also suggests that teriparatide treatment substantially reduced the increased risk of subsequent fracture in women who sustained a fracture during the FPT (P = .05). CONCLUSION: Vertebral fracture risk reduction by teriparatide administration persists for at least 18 months after discontinuation of therapy.

Osteoporosis and the global competition for health care resources.

Global aging superimposed on existing infectious diseases and trauma will aggravate competition for health care resources to diagnose and treat osteoporosis. Efforts to implement public health measures are needed, but the targeted approach to assessment and treatment of high-risk individuals must also be refined. Increases in the elderly population worldwide will cause a dramatic rise in osteoporotic fractures, but other age-related diseases will increase as well. Changes will be superimposed on existing public health problems (e.g., malaria, alcoholism), and these acute health care needs will take priority in some areas. Societies in most parts of the world may have to limit osteoporosis control to broad public health measures, and such efforts (e.g., calcium and vitamin D supplementation) should be supported. In these regions, clinical decision-making will generally be limited to treating patients with fractures (who presumably have already failed any public health measures in place), or in a few wealthy countries, to patients with low bone density identified by case-finding. Case-finding approaches will vary with the resources available, although unselective (mass) screening by bone densitometry is largely ineffective and unaffordable anywhere. The key to clinical decision-making on behalf of individuals will be an assessment of absolute fracture risk, and the tools needed to predict the risk of an osteoporotic fracture over the next 10 years are now being developed. These include bone density measures, but also incorporate other risk factors (e.g., fracture history, corticosteroid use), which may allow extension of fracture risk prediction to nonwhite populations and to men. Even with a universal risk prediction tool, cost-effective treatment thresholds will vary by country based on the level of fracture risk in the region and on the resources available for health care. To better compete for these resources, efforts should be made to lower the cost of osteoporosis interventions. Additionally, evidence is needed that these interventions are really effective in reducing fractures in the community.

Chronic idiopathic hyperphosphatasia: normalization of bone turnover with cyclical intravenous pamidronate therapy.

Chronic idiopathic hyperphosphatasia (CIH), or juvenile Paget disease, is a rare disorder characterized by increased bone turnover and progressive enlargement of bones. We report a girl, 6 1/2 years old, with a history of three fractures, short stature, delayed eruption of teeth, and poor hair growth. She had a waddling gait, bone deformities, kyphoscoliosis, hyperlordosis, genu valgum and curvature of her limbs. She also had progressive hearing loss but other cranial nerves were unaffected. Laboratory studies indicated high bone turnover: serum alkaline phosphatase: 4047 IU/l (normal value: 150-550), urinary hydroxyproline: 1205 mg/g creatinine (n.v.: 60-160), and urinary CrossLaps: 4360 microg/mmol creatinine (n.v.: 450-2100). Radiographs demonstrated generalized skeletal involvement with osteoectasia (expansion) of long bones, diffuse sclerosis, cotton wool appearance of the skull, absence of mastoid pneumatization, and crushed dorsal and lumbar vertebrae. Iliac crest biopsy was compatible with CIH. Cyclical intravenous pamidronate (1 mg/kg/day during 3 h, 3 consecutive days at 2- to 3-month intervals) was administered during 2 years with oral calcium 500 mg and vitamin D 1000 IU/day. Oral pamidronate was added after 11 months of i.v. therapy. Treatment-induced remarkable clinical and radiographic improvement with normalization of bone markers of osteoblastic and osteoclastic activity, including bone alkaline phosphatase, urinary hydroxyproline, and urinary CrossLaps.

Effect of intravenous pamidronate on bone markers and local bone mineral density in fibrous dysplasia.

Bisphosphonates have proven to be effective in patients with fibrous dysplasia of the bone (FD) as shown by their effect on bone pain, markers of bone turnover, or radiological changes. The aim of this study was to evaluate the usefulness of measuring bone mineral density (BMD) of affected bones to assess the efficacy of bisphosphonate treatment. Seven patients (mean age 26 years) received courses of 180 mg intravenous infusion of pamidronate every 6 months (60 mg/day during 3 days). Clinical symptoms, serum alkaline phosphatase, and urinary C-terminal cross-linking telopeptide of type I collagen were assessed every 3 months. BMD of total skeleton and X-rays of FD areas (FDa) were performed at baseline and at 12 months. BMD of FDa was compared with the contralateral side (CL) using the region of interest program on the total skeleton scan. BMD of total skeleton was normal at baseline. Average BMD of FDa was -11.4% compared with CL, a significantly greater difference than that observed between the left and right sides in healthy controls, -0.7% (P < 0.02). At 12 months bone pain diminished in all patients. Bone turnover markers decreased. Mean total skeleton BMD increased 3.3% (P < 0.02). Subregions of the total skeleton scan presenting FD lesions augmented: arms +9.6% (P < 0.02), legs +4.2%, and pelvis +3.5% (P < 0.05). The increase in mean BMD of FDa was +6.8% compared with +2.6% in CL. No changes were observed on the X-ray. These results indicate that simultaneous determination of markers of bone turnover and BMD of FDa is useful in short-term follow-up to determine the efficacy of intravenous pamidronate.

Bone densitometry of a patient with osteosclerosis.

A 30-yr-old Caucasian man with a history of dorsal and lumbar back pain, which responded partially to antiinflammatory agents, was seen at our Unit. The biochemical bone markers showed an increment in bone alkaline phosphatase and urinary CTX. Serum phosphate tended to be low. Radiographic abnormalities were marked osteosclerosis in the pelvis and vertebral bodies without changes in size. Bone scintigraphy results were normal. The increase in bone mineral density (BMD) was greater in L2-L4 (+ 3.9 SDs) than in total skeleton (+ 1.4 SDs). Analysis of skeletal subareas showed a marked increase in axial skeleton BMD: trunk, +4.0 SDs; spine, +2.5 SDs and pelvis, +4.5 SDs. BMD of the remaining subareas was found to be normal: skull, +0.04 SDs; arms, -0.3 SDs and legs, -0.05 SDs. The patient refused to have a bone biopsy. The radiologic, densitometric, and biochemical findings in the patient presented herein are compatible with axial osteomalacia. Evaluation of total skeleton BMD, and especially skeletal subareas, clearly indicated that the abnormal BMD was restricted to the spine and pelvis whereas the rest of the skeleton was not affected.

Is ultrasound of bone relevant for corticosteroid-treated patients? A comparative study with bone densitometry measured by DEXA.

Corticosteroid treatment diminishes bone mass and alters bone quality. The objective was to evaluate bone in corticosteroid-treated patients and controls and in fractured and non-fractured patients treated with corticosteroids using both X-ray densitometry (DEXA) and ultrasound. We evaluated 34 women aged 58 +/- 14 years (X +/- SD), who had been on long-term low dose prednisone therapy for at least 6 months, and who had never received specific treatment for osteoporosis. Bone mineral density of total skeleton (TS), lumbar spine (LS), femoral neck (FN), and vertebral morphometry (MXA) were measured by DEXA. Speed of sound (SOS), broadband ultrasound attenuation (BUA) and stiffness were measured using an Achilles Plus system. Forty-two healthy women served as controls. Both densitometric and ultrasound parameters in the patients were significantly diminished compared with controls: TS: P < 0.002, LS: P < 0.025, FS: P < 0.005, Stiffness: P < 0.001, BUA: P < 0.002 and SOS: P < 0.002. The percentage of patients with a Z score below -2 was higher in Stiffness and BUA: 38% and 47%, respectively, compared with a range of 16-24% in the other parameters (P < 0.05 BUA vs. DEXA measurements). Eleven patients with previous bone fracture had values lower than the non-fractured patients, both according to DEXA and ultrasound measurements, but the difference was only significant for BUA (P < 0.02). BUA of the calcaneus was more effective in detecting the specific skeletal alterations and fracture risk of the group of patients receiving chronic corticosteroid treatment.

Melatonin effects on bone: experimental facts and clinical perspectives.

Bone formation proceeds through a remodeling process that runs continuously, involving the resorption of old bone by osteoclasts, and the subsequent formation of new bone by osteoblasts. This is controlled by growth factors and cytokines produced in bone marrow microenvironment and by the action of systemic hormones, like parathyroid hormone, estradiol or growth hormone (GH). One candidate for hormonal modulation of osteoblast and osteoclast formation is melatonin. Because circulating melatonin declines with age, its possible involvement in post-menopausal and senescence osteoporosis is considered. This review article discusses early studies on melatonin-bone relationships and recent data that suggest a direct effect of melatonin on bone. Melatonin could act as an autacoid in bone cells as it is present in high quantities in bone marrow, where precursors of bone cells are located. Melatonin dose-dependently augmented proteins that are incorporated into the bone matrix, like procollagen type I c-peptide. Osteoprotegerin, an osteoblastic protein that inhibits the differentiation of osteoclasts is also augmented by melatonin in vitro. Another possible target cell for melatonin is the osteoclast, which degrades bone partly by generating free radicals. Melatonin through its free radical scavenger and antioxidant properties may impair osteoclast activity and bone resorption. At least in one study melatonin was both inhibitory to osteoclastic and osteoblastic cells. Therefore, the documented bone-protecting effect of melatonin in ovariectomized rats can depend in part on the free radical scavenging properties of melatonin. Additionally, melatonin may impair development of osteopenia associated with senescence by improving non-rapid eye movement sleep and restoring GH secretion. Whether melatonin can be used as a novel mode of therapy for augmenting bone mass in diseases deserves to be studied.

Melatonin increases oestradiol-induced bone formation in ovariectomized rats.

To assess the effect of melatonin on bone metabolism in ovariectomized rats, receiving oestradiol therapy or not, melatonin was administered in the drinking water (25 microg/mL water) and oestradiol (10 microg/kg body weight) or vehicle was given subcutaneously 5 days/week for up to 60 days after surgery. Urinary deoxypyridinoline (a marker of bone resorption) and circulating levels of bone alkaline phosphatase activity (a marker of bone formation), as well as serum calcium and phosphorus levels, were measured every 15 days. Bone area (BA), bone mineral content (BMC), bone mineral density (BMD) and total body fat (expressed as 100 g body weight) were measured by dual-energy X-ray absorptiometry at the end of the experiment. Body weight and total body fat were augmented after ovariectomy, and decreased after melatonin or oestradiol treatment. The effect of melatonin on body weight was seen in sham-operated rats only. Ovariectomy augmented, and melatonin or oestradiol lowered, urinary deoxypyridinoline excretion. This effect of melatonin and oestradiol was seen mainly in ovariectomized rats. The efficacy of oestradiol to counteract ovariectomy-induced bone resorption was increased by melatonin. Melatonin or oestradiol lowered serum bone alkaline phosphatase activity. Melatonin inhibition was seen mainly on the increase of bone alkaline phosphatase activity that followed ovariectomy. Serum phosphorus levels decreased after melatonin administration and were augmented after oestradiol injection; overall, melatonin impaired the increase of serum phosphorus caused by oestradiol. Ovariectomy decreased, and oestradiol increased, serum calcium levels while melatonin augmented serum calcium in sham-operated rats only. On day 60 after surgery, BMD and content decreased after ovariectomy and were increased after oestradiol injection. Melatonin augmented BA of spine and BMC of whole of the skeleton and tibia. The highest values observed were those of rats treated concurrently with oestradiol and melatonin. The present results indicate that: (i) melatonin treatment restrained bone remodelling after ovariectomy; (ii) the effect of melatonin required adequate concentrations of oestradiol; (iii) melatonin augmented oestradiol effects on bone in ovariectomized rats; (iv) a counter-regulation by melatonin of the increase in body fat caused by ovariectomy was uncovered. The melatonin doses employed were pharmacological in terms of circulating melatonin levels but not necessarily for some other fluids or tissues.

Osteoporosis en todas las hijas jovenes de una madre con multiples fracturas osteoporóticas: un caso de osteoporosis familiar / Osteoporosis in all young daughters of a mother with multiple osteoporotic fractures: a case of familiar osteoporosis

Se describe una familia, en la cual todos sus miembros mujeres, madre postmenopáusica (caso índice) y sus tres hijas premenopáusicas presentan osteoporosis. La madre (60 años) presentó fracturas axiales y periféricas, con una densidad mineral ósea (DMO) muy baja para su edad. Su abuela había sufrido una fractura de cadera. La hija mayor (30 años) sufrió múltiples fracturas vertebrales durante el embarazo y lactancia asociadas a una DMO muy baja. En consecuencia se estudiaron las dos hijas menores (29 y 27 años). En ellas se observó que la DMO estaba severamente disminuida (valores densitométricos de osteoporosis según la definición de la OMS) pero sin antecedentes de fracturas óseas. Es probable que la alta heredabilidad de la masa ósea sea la causa de la severa disminución de la DMO observada en todas las mujeres de esta familia, y responsable de fracturas óseas en dos de ellas. No hemos encontrado en la literatura descripciones de una familia similar, que muestre la importancia del estudio de la masa ósea de los descendientes de un individuo con osteoporosis severa, permitiendo la detección de familiares con baja masa ósea y alto riesgo de desarrollo de fracturas óseas