Bone area (BA) and bone mineral content (BMC) were measured from childhood to young adulthood at the total body (TB), lumbar spine (LS), total hip (TH), and femoral neck (FN). BA and BMC values were expressed as a percentage of young-adult values to determine if and when values reached a plateau. Data were aligned on biological ages [years from peak height velocity (PHV)] to control for maturity. TB BA increased significantly from À4 to þ4 years from PHV, with TB BMC reaching a plateau, on average, 2 years later at þ6 years from PHV (equates to 18 and 20 years of age in girls and boys, respectively). LS BA increased significantly from À4 years from PHV to þ3 years from PHV, whereas LS BMC increased until þ4 from PHV. FN BA increased between À4 and þ1 years from PHV, with FN BMC reaching a plateau, on average, 1 year later at þ2 years from PHV. In the circumpubertal years (À2 to þ2 years from PHV): 39% of the young-adult BMC was accrued at the TB in both males and females; 43% and 46% was accrued in males and females at the LS and TH, respectively; 33% (males and females) was accrued at the FN. In summary, we provide strong evidence that BA plateaus 1 to 2 years earlier than BMC. Depending on the skeletal site, peak bone mass occurs by the end of the second or early in the third decade of life. The data substantiate the importance of the circumpubertal years for accruing bone mineral. ß

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The accumulation of bone microdamage has been proposed as one factor that contributes to increased skeletal fragility with age and that may increase the risk for fracture in older women. This paper reviews the current status and understanding of microdamage physiology and its importance to skeletal fragility. Several questions are addressed: Does microdamage exist in vivo in bone? If it does, does it impair bone quality? Does microdamage accumulate with age, and is the accumulation of damage with age sufficient to cause a fracture? The nature of the damage repair mechanism is reviewed, and it is proposed that osteoporotic fracture may be a consequence of a positive feedback between damage accumulation and the increased remodeling space associated with repair. (J Bone Miner Res 1997;12:6-15)

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It has been hypothesized that suppression of bone remodeling allows microdamage to accumulate, leading to increased bone fragility. This study evaluated the effects of reduced bone turnover produced by bisphosphonates on microdamage accumulation and biomechanical properties of cortical bone in the dog rib. Thirty-six female beagles, 1-2 years old, were divided into three groups. The control group (CNT) was treated daily for 12 months with saline vehicle. The remaining two groups were treated daily with risedronate (RIS) at a dose of 0.5 mg/kg per day or alendronate (ALN) at 1.0 mg/kg per day orally. After sacrifice, the right ninth rib was assigned to cortical histomorphometry or microdamage analysis. The left ninth rib was tested to failure in three-point bending. Total cross-sectional bone area was significantly increased in both RIS and ALN compared with CNT, whereas cortical area did not differ significantly among groups. One-year treatment with RIS or ALN significantly suppressed intracortical remodeling (RIS, 53%; ALN, 68%) without impairment of mineralization and significantly increased microdamage accumulation in both RIS (155%) and ALN (322%) compared with CNT. Although bone strength and stiffness were not significantly affected by the treatments, bone toughness declined significantly in ALN (20%). Regression analysis showed a significant nonlinear relationship between suppressed intracortical bone remodeling and microdamage accumulation as well as a significant linear relationship between microdamage accumulation and reduced toughness. This study showed that suppression of bone turnover by high doses of bisphosphonates is associated with microdamage accumulation and reduced some mechanical properties of bone. (J Bone Miner Res 2000;15:613-620)

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Bone formation was measured in rat tibiae after 12 days of applied loading. Bending forces were applied using a four-point loading apparatus. Sham loads were applied at the same magnitudes as bending forces but the loading pads were arranged so that bending was minimized. Bending and sham loading were applied to the right tibiae of rats and the left tibiae served as contralateral controls. Loading was applied as a sine wave with a frequency of 2 Hz for 18 s (36 cycles) per day. The peak magnitude of applied load was 27, 33, 40, 52, and 64 N. Woven bone was observed on the periosteal surface in all animals subjected to loads of 40 N or greater. Periosteal woven bone formation occurred in both bending and sham loading groups. Woven bone formation on the periosteal surface was either absent or responded at a maximal rate if the stimulus threshold was surpassed. The amount of new woven bone and the woven bone-forming surface were independent of the magnitude of applied strain. Bone formation on the endocortical surface was exclusively lamellar. Lamellar bone formation was stimulated by applied bending of the tibia but not by sham loading. Bending strains above a loading threshold of 40 N or about 1050 mu strain increased both bone-forming surface and the mineral apposition rate and subsequently increased the bone formation rate as much as sixfold. No evidence of increased bone formation was seen for applied strains below 1050 mu strain. Examination of bulk stained sections from animals exposed to the highest applied loads showed no evidence of microcracks.(ABSTRACT TRUNCATED AT 250 WORDS)

When compact bone is subjected to bending loads, interstitial fluid in the bone matrix flows away from regions of high compressive stress. The amount of interstitial fluid flow is strongly influenced by the loading rate in a dose-dependent fashion. We hypothesize that interstitial fluid flow affects bone formation, and we tested this hypothesis indirectly by measuring the effect of different loading frequencies on bone formation rate in vivo. The right tibiae of adult female rats were subjected to applied bending at frequencies of 0.05, 0.1, 0.2, 0.5, 1.0, and 2.0 Hz for a 2-wk period. The rats were then killed and histomorphometric measurements of bone formation were made of the midshaft of the tibia. Bending of the tibia increased bone formation rate in the higher-frequency (0.5 to 2.0 Hz) loading groups as much as fourfold, yet no increase in bone formation rate was observed for loading frequencies below 0.5 Hz. In a separate experiment, we found stress-generated potentials (SGP) in the rat tibia to increase monotonically with increasing loading frequency. The dose-response relationship between loading frequency and the bone formation response closely resembles the relationship between loading frequency and SGP within bone. The qualitative similarity between these two relationships suggests that increased bone formation is associated with increased SGP, which are caused by interstitial fluid flow. Bone cells are known to be sensitive to electric fields and may respond directly to SGP. Also, fluid shear forces have been shown to stimulate bone cells in culture, so it is possible that increased interstitial fluid flow directly affects bone formation.