Comparison of rates of change in bone density as measured by dual-energy X-ray absorptiometry and quantitative computed tomography in osteoporotic females treated with fluoride.

We conducted a retrospective comparison of the rates of change in vertebral bone density measured by two densitometric techniques: dual-energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT) in osteoporotic women treated with fluoride. To compare both densitometric methods, lumbar vertebral bone density was determined before and during fluoride therapy in 104 osteoporotic women. All patients signed an informed consent under a protocol approved by our University Institutional Review Board. All subjects had at least three serial measurements using both densitometric techniques over the studied time period. Linear regression was used to calculate rate of change values for each patient. In agreement with previous published reports, lumbar density increased linearly over time both with DXA and QCT. Rates of change determined by DXA and QCT were significantly correlated (r = 0.88, p < 0.0001) and this relationship was independent of the magnitude of the increase in density. Either densitometric technique may be used to evaluate the axial skeletal response to fluoride therapy.

Serum fluoride and serum osteocalcin levels in response to a novel sustained-release monofluorophosphate preparation: comparison with plain monofluorophosphate.

In a previous study we found that sustained-release monofluorophosphate (MFP-SR), a novel, sustained-release MFP preparation, acutely maintained the basal therapeutic serum fluoride levels without causing the high serum peak levels associated with plain MFP administration. The objective of the present study was to determine (a) whether chronic MFP-SR administration would provide therapeutic serum fluoride levels, and (b) whether treatment with this new preparation would result in an increase in bone formation similar to that achieved with plain MFP. Bone formation was assessed by serum osteocalcin (OC) determination. We studied 17 postmenopausal women older than 60 years and suffering from primary osteoporosis. All had received a minimum of 6 months of continuous treatment with plain MFP at a dose of 152 mg/day (76 mg b.i.d.). Upon entering the study, the subjects were randomized, in a double-masked protocol, to receive either MFP-SR (76 mg b.i.d.) (n = 9) or placebo (n = 8) for 2 months, after which all subjects returned to the original plain MFP regimen. Serum fluoride and serum OC levels were determined monthly for 3 months. At the beginning of the study serum fluoride levels were in the accepted therapeutic range (5-10 microM) in all patients. Serum fluoride levels were maintained in the patients switched to MFP-SR. In contrast, serum fluoride levels decreased significantly (p < 0.005) in the placebo-treated control subjects and returned to therapeutic levels upon switching back to plain MFP. Similarly, serum OC levels remained elevated in the subjects switched to MFP-SR but dropped significantly (p < 0.001) in the placebo-treated group. Our results demonstrate that chronic MFP-SR administration, at a dose of 152 mg/day, results in maintenance of therapeutic serum fluoride levels and in stimulation of bone formation. Because we have previously reported that high, supratherapeutic post-absorptive serum fluoride levels are avoided by MFP-SR administration, this novel preparation may prevent side effects associated with plain MFP by reducing the amount of fluoride deposited in bone.

Effects of strength training on bone mineral density: hormonal and bone turnover relationships.

The effects of a 16-wk strength-training program on bone mineral density (BMD) was assessed by dual-energy X-ray absorptiometry in 21 men [age 61 +/- 1 (SE) yr]. Sixteen men (age 59 +/- 2 yr) served as control subjects. To investigate the possible hormonal relationships underlying the effects on BMD, serum concentrations of growth hormone, insulin-like growth factor I, and testosterone were determined before and after training. In addition, osteocalcin and skeletal alkaline phosphatase (markers of bone formation) and tartrate-resistant acid phosphatase (a marker of bone resorption) were measured before and after training to assess bone turnover. The training program resulted in a 2.8 +/- 0.6% increase in femoral neck BMD (1.004 +/- 0.037 vs. 1.031 +/- 0.037 g/cm2; P < 0.001). However, there were no significant changes in total body, anterioposterior spine, lateral spine, Ward's triangle, or greater trochanter BMD. Moreover, there were no significant changes in growth hormone, insulin-like growth factor I, testosterone, osteocalcin, or skeletal alkaline phosphatase. There were no changes in the control group. Thus, strength training can increase femoral neck BMD, and this effect does not appear to be accompanied by changes in anabolic hormones or markers of bone formation and resorption.

Strength training increases regional bone mineral density and bone remodeling in middle-aged and older men.

To determine the effects of strength training (ST) on bone mineral density (BMD) and bone remodeling, 18 previously inactive untrained males [mean age 59 +/- 2 (SE) yr] were studied before and after 16 wk of either ST (n = 11) or no exercise (inactive controls; n = 7). Total, spinal (L2-L4), and femoral neck BMD were measured in nine training and seven control subjects before and after the experimental period. Serum concentrations of osteocalcin, skeletal alkaline phosphatase isoenzyme, and tartrate-resistant acid phosphatase were measured before, during, and after the experimental program in all subjects. Training increased muscular strength by an average of 45 +/- 3% (P < 0.001) on a three-repetition maximum test and by 32 +/- 4% (P < 0.001) on an isokinetic test of the knee extensors performed at 60 degrees/s. BMD increased in the femoral neck by 3.8 +/- 1.0% (0.900 +/- 0.05 vs. 0.933 +/- 0.05 g/cm2, P < 0.05) and in the lumbar spine by 2.0 +/- 0.9% (1.180 +/- 0.06 vs. 1.203 +/- 0.06 g/cm2, P < 0.05). However, changes in lumbar spine BMD were not significantly different from those in the control group. There was no significant change in total body BMD. Osteocalcin increased by 19 +/- 6% after 12 wk of training (P < 0.05) and remained significantly elevated after 16 wk of training (P < 0.05). There was a 26 +/- 11% increase in skeletal alkaline phosphatase isoenzyme levels (P < 0.05) after 16 wk of training.(ABSTRACT TRUNCATED AT 250 WORDS)

Prevention and treatment of glucocorticoid-induced osteoporosis. A pathogenetic perspective.

Since the discovery of cortisol and the synthesis of related compounds, these potent pharmacologic agents have been progressively more widely utilized in allergic, pulmonary, and rheumatologic conditions. Organ transplantation represents a new group of patients added to the already large pool of subjects receiving glucocorticoids. However, glucocorticoids cause major side effects involving several organ systems, including the cardiovascular, endocrine, gastrointestinal, ophthalmologic, and musculoskeletal systems. Among the most dramatic side effects is the development of glucocorticoid-induced osteoporosis. Glucocorticoid use in the treatment of chronic obstructive pulmonary disease accounts for the majority of male patients with osteoporosis seen in our mineral metabolism clinic. This article focuses on glucocorticoid-induced osteoporosis in the adult with an emphasis on the clinical aspects of this condition. It is intended not as an extensive review on the subject but as a practical guide to help clinicians prevent and treat this condition in adult patients.

Spinal fractures during fluoride therapy for osteoporosis: relationship to spinal bone density.

Recent studies report that fluoride therapy for osteoporosis increases spinal bone density without improving vertebral fracture rate, challenging the notion that restoration of bone mass improves bone fragility. To further evaluate this issue, the relationship between spinal bone density and vertebral fracture rate was examined in a large number of fluoride-treated, osteoporotic patients. A retrospective assessment was made of clinical data collected from our observations of 389 osteoporotics treated with fluoride 30 +/- 8 mg/day (mean +/- SD) (equivalent to 66 +/- 17 mg NaF/day) and calcium 1500 mg/day for 28 +/- 18 months. Fracture rate and bone density were assessed in the same region of the spine (i.e., T12 through L4) using quantitative computed tomography (QCT). Spinal bone density increased with time on fluoride, but the relationship was hyperbolic (r = 0.99, p less than 0.0001; asymptote = 167 mg/cc on double-reciprocal plot), suggesting a plateau in the response. The spinal fracture rate decreased as a function of time on therapy (r = -0.83, p less than 0.01), and was inversely related to spinal bone density during fluoride therapy (r = 0.70, p less than 0.001 on arithmetic plot; r = -0.79, p less than 0.001 on semi-log plot). The subgroup of patients who responded to treatment with a significant increase in spinal bone density had a 48% reduction in spinal fracture rate compared with non-responders (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Hip mineral density in females with a recent hip fracture.

To evaluate the role of local bone mineral density (BMD) in the etiology of hip fractures, we measured the hip BMD using dual photon absorptiometry in 29 females who had recently suffered a hip fracture associated with minimal or moderate, but not major, trauma and compared their BMD to those of 14 young normal females, 58 early postmenopausal normal females, 13 age-matched normal females, and 114 spinal osteoporotic females without a hip fracture. Hip-fractured patients had a BMD significantly lower (P less than 0.001) than that of all other studied groups, suggesting that a low hip BMD is associated with hip fracture risk. A femoral neck BMD below 0.75 g/cm2 suggests an increased likelihood for developing a hip fracture. Peak BMD was measured at 1.03 g/cm2, a value comparable to published normative data. Thus, a loss in hip BMD of approximately 30% from peak mineral density appears necessary before a hip fracture may occur after moderate trauma.

Fluoride therapy for osteoporosis: a review of dose response, duration of treatment, and skeletal sites of action.

Osteoporosis is a disease characterized by a reduction in bone density which predisposes to fracture after even minimal trauma. Fluoride, because it has consistently been shown to stimulate bone formation and increase trabecular bone density, has been widely studied for the treatment of osteoporosis. The article focuses on the dose response, duration of treatment, and skeletal sites of action of fluoride; we also include comments on the effect of fluoride on vertebral and appendicular fracture rates. The skeletal response to fluoride doses, ranging from 15 to 43 mg elemental fluoride per day, included a linear increase in spinal bone density at an average rate of 1.25 +/- 0.91 mg/cm3 per month. The rate of increase in spinal bone density was related to the dose of fluoride (r = 0.34, P less than 0.03). Spinal bone density had increased above the fracture threshold in 44% of patients treated with fluoride for 32 +/- 10 months. The time required to achieve this goal was, however, influenced by the pretreatment spinal bone density and interpatient variation in response to fluoride treatment. Patients whose spinal bone density remained below the fracture threshold had lower pretreatment bone densities and/or slower rates of increase in spinal bone density (P less than 0.001). The osteogenic effect of fluoride was not limited to the spine. After 2 years of fluoride therapy, we found bone density in the femoral condyle (measured by QCT) to have increased by 13 +/- 2.6 mg/cm3 (n = 38, P less than 0.001); bone density in the hip (measured by DPA) was increased by 0.0261 +/- 0.015 g/cm2 (n = 55, P less than 0.025).(ABSTRACT TRUNCATED AT 250 WORDS)

Fluoride therapy for osteoporosis promotes a progressive increase in spinal bone density.

Since osteoporosis is a disease of diminished bone density, and since osteoporotic fractures occur most commonly in the spine, the ideal therapeutic agent for osteoporosis is one which can increase spinal bone density and thereby reduce the risk for vertebral fractures. In the current study we sought to examine the effect of fluoride therapy on spinal bone density utilizing quantitative computed tomography to measure changes in vertebral trabecular bone density during treatment with fluoride. A group of 61 postmenopausal osteoporotic females, aged 70 +/- 9 years, were treated with 34 +/- 7 mg elemental fluoride/day (equivalent to 75 +/- 15 mg NaF/day) and 1500 mg calcium/day for 19 +/- 6 months. Spinal bone density was increased within the first 6 months of fluoride therapy by 42% or 10 +/- 13 mg/cm3 (p less than 0.001) and continued to increased throughout 2 years of observation. The skeletal response to fluoride therapy was also associated with an early increase in serum alkaline phosphatase activity (p less than 0.001), which was related to the increase in spinal bone density (r = .58, p less than 0.001). Large interpatient variation was observed in the spinal bone response to fluoride therapy, which was not explained by variations in the pretreatment spinal bone density (r = .04), age of the patient (r = .15), or dose of fluoride (r = .16). Results from these studies demonstrate (1) the therapeutic value of fluoride to increase trabecular bone density linearly for 2 years in the osteoporotic spine and (2) the clinical value of measuring spinal bone density and/or serum alkaline phosphatase activity as indices of the skeletal response to fluoride.

Efficacy of long-term fluoride and calcium therapy in correcting the deficit of spinal bone density in osteoporosis.

Long-term fluoride therapy for osteoporosis has been shown to increase the thickness of vertebral trabeculae as seen on spinal radiographs. To determine if this qualitative finding represents a measurable increase in spinal bone density, quantitative computed tomography was utilized to measure trabecular vertebral body density (TVBD) in the lumbar spine of 18 female osteoporotic patients, all of whom had been treated with sodium fluoride, 77 +/- 13 mg/day (mean +/- SD), and calcium, 1000 mg/day, for 57 +/- 24 months. TVBD in these fluoride treated osteoporotic patients (132 +/- 82 mg/cm3) was found to be significantly greater than mean TVBD for an age-matched group of untreated female osteoporotic patients (51 +/- 21 mg/cm3, n = 89, p less than 0.001). The value for TVBD in the long-term fluoride treated osteoporotics was not only similar to previously published values for TVBD (104 +/- 30 mg cm3) in normal females of similar age, but was also above the calculated TVBD "fracture threshold" of 100 mg/cm3 for females. Only one of the 18 fluoride treated osteoporotics continued to have spinal fractures during therapy, accounting for 4 fractures per 87.2 patient years of observation, a value which is significantly lower than the published incidence of 76 fractures per 91 patient years for untreated osteoporotic patients (p less than 0.001). Together, these findings demonstrate that long-term fluoride and calcium therapy for osteoporosis increases TVBD in the majority of patients within a reasonable time frame and significantly reduces the risk for spinal fractures.(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship between trabecular vertebral body density and fractures: a quantitative definition of spinal osteoporosis.

To evaluate the relationship between vertebral fractures and trabecular vertebral body density (TVBD), as measured by computed tomography (CT), we evaluated 110 female and 38 male patients referred consecutively to our clinic for an osteoporosis evaluation. Number of fractures per patient and TVBD was negatively correlated in both males and females (r = -.64, P less than .001 and r = -.69, P less than .001, respectively). Based on this relationship and that between percent of patients with fracture and TVBD, we devised four different approaches to calculate the fracture threshold. (1) Because the x-axis intercept of this regression line represents the TVBD value at zero fractures, this intercept can be considered the fracture threshold, which was 103 mg/cm3 for females and 132 mg/cm3 for males. (2) Breakpoint analysis of the relationship between the number of vertebral fractures per patient v TVBD gave a fracture threshold value of 98 mg/cm3 for females, but for males we were unable to compute a threshold value because of the small sample size. The percentage of patients with fractures was also negatively correlated with TVBD for males and females (r = -.98, P less than .001, and r = -.94, P less than .001, respectively). (3) the x-axis intercept of this relationship, which represents the fracture threshold, was 123 mg/cm3 for males and 101 mg/cm3 for females. (4) The fracture threshold, calculated as the mean TVBD + 2 SD for patients with fracture(s), was 120 and 92 mg/cm3 for males and females, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Vertebral bone density in children: effect of puberty.

To determine changes in bone density during growth, trabecular vertebral density and an index of spinal cortical bone were measured with quantitative computed tomography in 101 children. The children were divided by age into three groups: prepubertal, indeterminate, and pubertal. Compared with prepubertal children, pubertal adolescents had significantly higher trabecular bone density and more compact bone in the spine (P less than .001). After controlling for puberty, vertebral bone density failed to correlate significantly with age, sex, weight, height, surface area, and body mass index. The results indicate that bone density increases markedly during puberty.

Skeletal scintigraphic changes in osteoporosis treated with sodium fluoride: concise communication.

An appendicular skeletal response to sodium fluoride (NaF) was detected by total skeletal scintigrams. Twelve postmenopausal osteoporotic women were treated with NaF (88 mg/day) and calcium (1500 mg/day). Total skeletal scintigrams were obtained before and during treatment. Within 4 to 21 mo (mean: 8.3), all 12 patients showed new areas of increased uptake corresponding to metaphyseal regions and short bones of the appendicular skeleton. The number of peripheral bones involved in each subject ranged from four to 12. The most frequently involved sites (11 of 12 patients) were the right distal femur and proximal tibia. Nine patients showed an increase in serum alkaline phosphatase activity, which was attributed to an increase in the skeletal isoenzyme. Seven of 12 patients developed bone pain in one or more of the regions of increased uptake. This study establishes that the skeletal scintigram is a sensitive index of the peripheral skeletal response to NaF.